Pharmacokinetic study of four orally formulated combinations of acetaminophen and ibuprofen in healthy volunteers under fasting conditions

• Register: ANZCTR
• Last refreshed on: 13 January 2020
• Main ID: ACTRN12616000418471
• Date of registration: 01/04/2016
• Prospective Registration: Yes
• Primary sponsor: AFT Pharmaceuticals Ltd
• Public title: Pharmacokinetic study of four orally formulated combinations of acetaminophen and ibuprofen in healthy volunteers under fasting conditions
• Scientific title: A single dose, four-way, open-label study to determine the pharmacokinetics and bioavailability of an oral suspension of combined acetaminophen and ibuprofen, a powder sachet of combined acetaminophen and ibuprofen for oral solution and two tablet formulations of combined acetaminophen and ibuprofen in 28 healthy volunteers under fasting conditions.
• Date of first enrolment: 14/07/2016
• Target sample size: 28
• Recruitment status: Completed
• URL: https://anzctr.org.au/ACTRN12616000418471.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Open (masking not used);Assignment: Crossover;Type of endpoint: Pharmacokinetics;
• Phase: Phase 1

Countries of recruitment

Jordan

Contacts

• Name: Dr Hartley Atkinson

• Name: Dr Hartley Atkinson

Key inclusion & exclusion criteria

Inclusion criteria: Healthy subjects, males and females aged 18 to 50 years of age.
Females must be sterile or using adequate contraception.
Participants must not have taken any prescription medications for at least 14 days or over-the-counter medications for at least 3 days before the start of each study phase, with the exception of oral contraceptives and the study medication.
All subjects must be deemed healthy on the basis of a medical history, physical exam (including vital signs and 12-lead ECG recording), urinalysis, and blood biochemical, haematological and serological examinations.
Exclusion criteria: Women who are pregnant, nursing, unwilling to take adequate contraceptive precautions or undergo a urine pregnancy test
Excess weekly alcohol consumption
History of drug abuse
Smoking > 10 cigarettes per day
Unwilling to abstain from smoking throughout duration of the study
Unable to abstain from prescription drugs within 14 days prior to the study, vitamins within 2 days prior to the study, grapefruit containing foods or beverages within 7 days prior to the study or caffeine containing foods or beverages within 24 hours prior to the study
Used OTC herbal products within 3 days prior to the study
Participating in another clinical trial within 80 days
Clinically significant abnormal laboratory tests.

Age minimum: 18 Years
Age maximum: 50 Years
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Pain relief;
Pain relief

Anaesthesiology - Pain management

Intervention(s)

Each participant will be randomly allocated to receive a single dose of each of the following treatments in a four-way cross-over sequence:
- Treatment A: oral suspension containing 1000 mg acetaminophen + 300 mg ibuprofen in 31.25 mL
- Treatment B: powder sachet containing 1000 mg acetaminophen + 300 mg ibuprofen for oral solution
- Treatment C: tablets providing total dose of 1000 mg acetaminophen + 300 mg ibuprofen
- Treatment D: tablets providing total dose of 975 mg acetaminophen + 292.5 mg ibuprofen

The administration of doses will be supervised on site.
All treatments will be administered under fasting conditions. Participants will be fasted for at least 10 hours overnight before dosing and for 3 hours after dosing. Water will be restricted for 1 hour pre-dose and 1 hour post-dose (with the exception of water administered as part of dosing).

Administration
- Oral Suspension formulation: 31.25 mL of the oral suspension will be dispensed for consumption. Any residue remaining after initial administration will be resuspended with 240 mL of water and consumed.
- Powder Sachet formulation: contents of the sachet will be dissolved in 240 mL hot water and consumed once cold.
- Tablet Formulations: will be administered with 240 mL of water.

Dose-frequency is single doses of four different formulations separated by a washout period of 3 days.
All participants will complete the four periods in cross-over fashion.

Primary Outcome(s)

To determine the pharmacokinetic parameters (Cmax, AUC(0-t), AUC(0-inf), Tmax, Kel, t1/2) of acetaminophen and ibuprofen and compare between four treatment groups, under fasting conditions. [Single-dose study measuring plasma concentration of acetaminophen and ibuprofen pre-dose and at 5, 15, 30, 45 minutes and 1.00, 1.25, 1.50, 2.00, 3.00, 6.00, 8.00, 10.00 and 12.00 hours after study drug administration. ]

Secondary Outcome(s)

An acute safety evaluation will be performed during each study period by recording spontaneously reported adverse events and by clinical assessments.
Known NSAID adverse effects (i.e. GI ulceration, indigestion/stomach pain, GI bleeding, bronchospasm, water retention, renal failure, skin reactions and thromboembolic events), and known adverse effects of acetaminophen (i.e. clinical evidence of hepatotoxicity) will be compared between groups.
Adverse events will continue to be assessed up to 7 days after the last dose of the study medication by spontaneous reporting and at a final follow-up phone call.
[Safety will be evaluated during each study period (from administration to 12 hours post administration for each formulation), and for 7 days following study drug administration. ]

Secondary ID(s)

AFT-MX-14A

Source(s) of Monetary Support

AFT Pharmaceuticals Ltd

Ethics review

Status: Approved
Approval date:
Contact:

International Pharmaceutical Research Centre (IPRC)

Results

• Results available: Yes
• Date Posted: 20/12/2018
• Date Completed: 04/08/2016